Tutorial

Methylmalonyl CoA mutase catalyzes one of only two known B12-requiring reactions, and the only one to occur in mitochondria. B12 must first be converted to its adenosyl-B12 form before it can serve as a cofactor for this enzyme. Disruption of this reaction leads directly to methylmalonic aciduria, with associated neurological symptoms and learning deficiencies. A contributing factor may be a secondary backup of propionyl CoA which may substitute for acetyl CoA in the citrate synthase reaction to form methyl citrate, a TCA cycle poison. Presumably, this scenario is particularly serious for neural tissue due to its high oxidative demands. Now on to folate metabolism...